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Volume 17
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Article

Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis

by
Yuki Minayoshi
1,†,
Hitoshi Maeda
1,*,†,
Keisuke Hamasaki
1,
Taisei Nagasaki
1,
Mei Takano
1,
Ryo Fukuda
1,
Yuki Mizuta
1,
Motohiko Tanaka
2,3,
Yutaka Sasaki
2,4,
Masaki Otagiri
5,6,
Hiroshi Watanabe
1 and
Toru Maruyama
1,*
1
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto 862-0973, Japan
2
Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan
3
Public Health and Welfare Bureau, 5-1-1 Oe, Chuo-ku, Kumamoto 862-0971, Japan
4
Osaka Central Hospital, 3-3-30 Umeda, Kita-ku, Osaka 530-0001, Japan
5
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
6
DDS Research Institute, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceuticals 2024, 17(2), 260; https://doi.org/10.3390/ph17020260
Submission received: 31 December 2023 / Revised: 3 February 2024 / Accepted: 7 February 2024 / Published: 19 February 2024
(This article belongs to the Special Issue Molecular Modification in Designing Next Generation Drug Delivery Systems)
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Abstract

Although a lot of effort has been put into creating drugs and combination therapies against chronic hepatitis, no effective treatment has been established. Type-I interferon is a promising therapeutic for chronic hepatitis due to its excellent anti-inflammatory effects through interferon receptors on hepatic macrophages. To develop a type-I IFN equipped with the ability to target hepatic macrophages through the macrophage mannose receptor, the present study designed a mouse type-I interferon-mannosylated albumin fusion protein using site-specific mutagenesis and albumin fusion technology. This fusion protein exhibited the induction of anti-inflammatory molecules, such as IL-10, IL-1Ra, and PD-1, in RAW264.7 cells, or hepatoprotective effects on carbon tetrachloride-induced chronic hepatitis mice. As expected, such biological and hepatoprotective actions were significantly superior to those of human fusion proteins. Furthermore, the repeated administration of mouse fusion protein to carbon tetrachloride-induced chronic hepatitis mice clearly suppressed the area of liver fibrosis and hepatic hydroxyproline contents, not only with a reduction in the levels of inflammatory cytokine (TNF-α) and fibrosis-related genes (TGF-β, Fibronectin, Snail, and Collagen 1α2), but also with a shift in the hepatic macrophage phenotype from inflammatory to anti-inflammatory. Therefore, type-I interferon-mannosylated albumin fusion protein has the potential as a new therapeutic agent for chronic hepatitis.
Keywords: type-I interferon; mannose receptor; Kupffer cells; albumin fusion technology; site-specific mutagenesis; species difference type-I interferon; mannose receptor; Kupffer cells; albumin fusion technology; site-specific mutagenesis; species difference

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MDPI and ACS Style

Minayoshi, Y.; Maeda, H.; Hamasaki, K.; Nagasaki, T.; Takano, M.; Fukuda, R.; Mizuta, Y.; Tanaka, M.; Sasaki, Y.; Otagiri, M.; et al. Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis. Pharmaceuticals 2024, 17, 260. https://doi.org/10.3390/ph17020260

AMA Style

Minayoshi Y, Maeda H, Hamasaki K, Nagasaki T, Takano M, Fukuda R, Mizuta Y, Tanaka M, Sasaki Y, Otagiri M, et al. Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis. Pharmaceuticals. 2024; 17(2):260. https://doi.org/10.3390/ph17020260

Chicago/Turabian Style

Minayoshi, Yuki, Hitoshi Maeda, Keisuke Hamasaki, Taisei Nagasaki, Mei Takano, Ryo Fukuda, Yuki Mizuta, Motohiko Tanaka, Yutaka Sasaki, Masaki Otagiri, and et al. 2024. "Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis" Pharmaceuticals 17, no. 2: 260. https://doi.org/10.3390/ph17020260

APA Style

Minayoshi, Y., Maeda, H., Hamasaki, K., Nagasaki, T., Takano, M., Fukuda, R., Mizuta, Y., Tanaka, M., Sasaki, Y., Otagiri, M., Watanabe, H., & Maruyama, T. (2024). Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis. Pharmaceuticals, 17(2), 260. https://doi.org/10.3390/ph17020260

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